Toxicity and human health assessment of an alcohol-to-jet (ATJ) synthetic kerosene.

A toxicological investigation was conducted for alcohol-to-jet (ATJ) fuels intended as a 50:50 blend with petroleum-derived fuel Jet Propulsion (JP)-8. The ATJ synthetic paraffinic kerosene (SPK) fuel was produced by Gevo (Englewood CO) and derived either from biomass (bio) or non-biomass sources. All toxicity tests were performed with one or both ATJ fuels following addition of a standard additive package required for JP-8. The primary fuel, Gevo (bio) ATJ SPK produced from biomass-derived iso-butanol, exhibited the same dermal irritation potential in rabbits as JP-8; the non-biomass-derived fuel was less irritating. The Gevo (bio) fuel was non-clastogenic in micronucleus testing with rats and neither version was mutagenic in the bacterial reverse mutation assay. A 90-day study was performed with Gevo (bio) ATJ SPK by exposing male and female Fischer 344 rats to target concentrations of 0, 200, 700 or 2000 mg/m3 of fuel, 6 hr per day, 5 days a week for 69 exposure days and included neurobehavioral assays and reproductive health evaluations in the study design. Results were negative or limited to irritant effects in the respiratory system due to exposure to a vapor and aerosol mixture in the 2000 mg/m3 exposure group. Occupational exposure limits for JP-8 were proposed for these ATJ fuels since these fuels display similar or somewhat lower toxicity than JP-8. As both versions of the Gevo ATJ jet fuel were similar, handling of either fuel alone or in a blend with petroleum-derived JP-8 appears unlikely to increase human health risks for workers.

Toxicity and occupational exposure assessment for hydroprocessed esters and fatty acids (HEFA) alternative jet fuels.

The U.S. Air Force (USAF) has pursued development of alternative fuels to augment or replace petroleum-based jet fuels. Hydroprocessed esters and fatty acids (HEFA) renewable jet fuel is certified for use in commercial and USAF aircraft. HEFA feedstocks include camelina seed oil (Camelina sativa, HEFA-C); rendered animal fat (tallow, HEFA-T); and mixed fats and oils (HEFA-F). The aim of this study was to examine potential toxic effects associated with HEFA fuels exposures. All 3 HEFA fuels were less dermally irritating to rabbits than petroleum-derived JP-8 currently in use. Inhalation studies using male and female Fischer-344 rats included acute (1 day, with and without an 11-day recovery), 5-, 10- or 90-day durations. Rats were exposed to 0, 200, 700 or 2000 mg/m3 HEFA-F (6 hr/day, 5 days/week). Acute, 5 - and 10-day responses included minor urinalysis effects. Kidney weight increases might be attributed to male rat specific hyaline droplet formation. Nasal cavity changes included olfactory epithelial degeneration at 2000 mg/m3. Alveolar inflammation was observed at ≥700 mg/m3. For the 90-day study using HEFA-C, no significant neurobehavioral effects were detected. Minimal histopathological effects at 2000 mg/m3 included nasal epithelium goblet cell hyperplasia and olfactory epithelium degeneration. A concurrent micronucleus test was negative for evidence of genotoxicity. All HEFA fuels were negative for mutagenicity (Ames test). Sensory irritation (RD50) values were determined to be 9578 mg/m3 for HEFA-C and greater than 10,000 mg/m3 for HEFA-T and HEFA-F in male Swiss-Webster mice. Overall, HEFA jet fuel was less toxic than JP-8. Occupational exposure levels of 200 mg/m3 for vapor and 5 mg/m3 for aerosol are recommended for HEFA-based jet fuels.

Toxicity and occupational exposure assessment for Fischer-Tropsch synthetic paraffinic kerosene.

Fischer-Tropsch (FT) Synthetic Paraffinic Kerosene (SPK) jet fuel is a synthetic organic mixture intended to augment petroleum-derived JP-8 jet fuel use by the U.S. armed forces. The FT SPK testing program goal was to develop a comparative toxicity database with petroleum-derived jet fuels that may be used to calculate an occupational exposure limit (OEL). Toxicity investigations included the dermal irritation test (FT vs. JP-8 vs. 50:50 blend), 2 in vitro genotoxicity tests, acute inhalation study, short-term (2-week) inhalation range finder study with measurement of bone marrow micronuclei, 90-day inhalation toxicity, and sensory irritation assay. Dermal irritation was slight to moderate. All genotoxicity studies were negative. An acute inhalation study with F344 rats exposed at 2000 mg/m3 for 4 hr resulted in no abnormal clinical observations. Based on a 2-week range-finder, F344 rats were exposed for 6 hr per day, 5 days per week, for 90 days to an aerosol-vapor mixture of FT SPK jet fuel (0, 200, 700 or 2000 mg/m3). Effects on the nasal cavities were minimal (700 mg/m3) to mild (2000 mg/m3); only high exposure produced multifocal inflammatory cell infiltration in rat lungs (both genders). The RD50 (50% respiratory rate depression) value for the sensory irritation assay, calculated to be 10,939 mg/m3, indicated the FT SPK fuel is less irritating than JP-8. Based upon the proposed use as a 50:50 blend with JP-8, a FT SPK jet fuel OEL is recommended at 200 mg/m3 vapor and 5 mg/m3 aerosol, in concurrence with the current JP-8 OEL.

Reciprocal translocations in somatic and germ cells of mice chronically exposed by inhalation to ethylene oxide: implications for risk assessment.

Groups of male B6C3F1 mice were exposed by inhalation to 0, 25, 50, 100 or 200 p.p.m. ethylene oxide (EO) for up to 48 weeks (6 hours/day, 5 days/week). Animals were sacrificed at 6, 12, 24 and 48 weeks after the start of the exposure for analyses of reciprocal translocations in peripheral blood lymphocytes and germ cells. The frequency of the total chromosomal aberrations in the peripheral blood lymphocytes was significantly increased at the 100 and 200 p.p.m. exposure concentrations at the 12-week time point, at 50, 100 and 200 p.p.m. at the 24-week time point and at all EO concentrations at the 48-week time point. The frequency of stable reciprocal translocations, which can be used as biomarkers, was increased (P < 0.05) at 100 and 200 p.p.m. at the 12-week time point, at 100 and 200 p.p.m. at the 24-week time point and at 50, 100 and 200 p.p.m. at the 48-week time point. No statistically significant increase could be observed in translocation frequencies at the 6-week time point in the peripheral blood lymphocytes. The exposure-response curves were non-linear when the frequencies of translocations were plotted against EO exposure durations or against EO exposure concentrations. There was no effect of exposure concentration rate on reciprocal translocation frequency. Reciprocal translocations induced in spermatogonial stem cells (observed at the sprematocyte stage) showed significant increases in translocation frequencies over controls at all EO concentrations at 48 weeks. However, increases were small and they did not occur in a dose-responsive manner. The statistically significant increase observed at 12 weeks in the spermatocytes was equivocal. This study provides low-level chronic exposure somatic cytogenetic data generated in mice that can be used to support the shape of the tumour dose-response in rodents and humans The germ cell cytogenetic data are discussed in terms of its relevance for a threshold response for genetic effects at low exposures.

Meeting report: hazard assessment for nanoparticles--report from an interdisciplinary workshop.

In this report we present the findings from a nanotoxicology workshop held 6-7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders.